IF 2.6 3区生物学 Q2 GENETICS & HEREDITY

Gene

Pub Date : 2024-10-22 DOI: 10.1016/j.gene.2024.149030

Yang-Liu Zhou , Tao Meng , Li Zhang , Na Xu , Mingya Yang , Yan Zhang , Zhenzhen Wang , Yu Liu , Anqi Han , Jiawei Zuo , Haiyi Sun , Chao Zhang , Li-Xin Zhu

Objective

The transcription factor MAFB is part of the MAF family and is known to promote hepatocellular carcinoma (HCC) by upregulating cyclin D1. However, its role in HCC immunity and prognosis remains unclear. This study explores the biological function, prognostic significance, and immune impact of MAFB in HCC.

Methods

Immunohistochemistry was used to analyze MAFB expression in HCC and adjacent non-tumor tissues. RT-qPCR and Western blotting measured MAFB levels in HCC cell lines. Specific siRNA was used to knockdown MAFB in HCCLM3 and MHCC97H cells, followed by assays to evaluate cell proliferation, migration, and colony formation. Data from the TCGA database and online tools TIMER and TISDB were used to assess the relationship between MAFB and immune responses. A prognostic model based on MAFB-related immune genes was established, and drug sensitivity analysis was performed.

Results

MAFB was significantly overexpressed in HCC tissues. Knockdown of MAFB in HCC cell lines reduced their proliferation and migration abilities. The risk model based on MAFB-related immune genes effectively predicted patient prognosis, supported by ROC curves. Gene set enrichment analysis indicated that MAFB is involved in immune-related pathways. Several drugs were identified as potentially sensitive to MAFB expression levels.

Conclusion

MAFB plays a significant role in HCC development and immune regulation. The prognostic model combining MAFB-related immune genes provides valuable insights for predicting patient outcomes and identifying potential therapeutic targets.

目的转录因子 MAFB 是 MAF 家族的一部分，已知它能通过上调细胞周期蛋白 D1 促进肝细胞癌（HCC）的发生。然而，它在 HCC 免疫和预后中的作用仍不清楚。本研究探讨了MAFB在HCC中的生物学功能、预后意义和免疫影响：方法：采用免疫组化方法分析 MAFB 在 HCC 和邻近非肿瘤组织中的表达。RT-qPCR和Western印迹检测了HCC细胞系中MAFB的水平。使用特异性 siRNA 敲除 HCCLM3 和 MHCC97H 细胞中的 MAFB，然后进行细胞增殖、迁移和集落形成评估。TCGA数据库和在线工具TIMER与TISDB中的数据被用来评估MAFB与免疫反应之间的关系。建立了基于MAFB相关免疫基因的预后模型，并进行了药物敏感性分析：结果：MAFB在HCC组织中明显过表达。结果：MAFB在HCC组织中明显高表达，在HCC细胞系中敲除MAFB可降低其增殖和迁移能力。基于MAFB相关免疫基因的风险模型能有效预测患者的预后，并得到ROC曲线的支持。基因集富集分析表明，MAFB参与了免疫相关通路。结论：MAFB在免疫相关通路中起着重要作用：结论：MAFB在HCC的发展和免疫调节中起着重要作用。结合 MAFB 相关免疫基因的预后模型为预测患者预后和确定潜在治疗靶点提供了有价值的见解。

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引用次数: 0

Optimal control analysis on the spread of COVID-19: Impact of contact transmission and environmental contamination. COVID-19 传播的优化控制分析：接触传播和环境污染的影响。

IF 2.6 3区生物学 Q2 GENETICS & HEREDITY

Gene

Pub Date : 2024-10-22 DOI: 10.1016/j.gene.2024.149033

Sunil Singh Negi, Ravina, Nitin Sharma, Anupam Priyadarshi

The study investigates the intricate dynamics of SARS-CoV-2 transmission, with a particular focus on both close-contact interactions and environmental factors. Using advanced mathematical modeling and epidemiological analysis, explored the effects of these transmission pathways on the spread of COVID-19. The equilibrium points for both the disease-free and endemic states calculated and evaluated their global stability. Additionally, the basic reproduction number (R₀) is derived to quantify the transmission potential of the virus. To ensure model accuracy, numerical simulations are performed using MATLAB, utilizing daily COVID-19 case data from India. Parameter values are sourced from existing literature, with certain parameters estimated through fitting the model to observed data. Crucially, the model incorporates environmental transmission factors, such as surface contamination and airborne spread. The inclusion of these factors provides a more comprehensive understanding of the virus's spread, demonstrating the importance of interventions like use of face masks, environmental sanitization, vaccine efficacy, availability of treatment resources underappreciated when focusing solely on direct human contact. A sensitivity analysis is conducted to assess the impact of different parameters on R₀, with results visualized through heat maps to identify the most influential factors. Furthermore, Pontryagin's maximum principle is employed to develop an optimal control model, enabling the formulation of effective intervention strategies. By analysing both interpersonal and environmental transmission mechanisms, this study offers a more holistic framework for understanding SARS-CoV-2 transmission. The insights gained are critical for informing public health strategies, emphasizing the necessity of addressing both direct contact and environmental sources of infection to more effectively manage current and future outbreaks.

该研究调查了 SARS-CoV-2 传播的复杂动态，尤其关注密切接触者之间的相互作用和环境因素。利用先进的数学建模和流行病学分析，探讨了这些传播途径对 COVID-19 传播的影响。计算了无病状态和流行状态的平衡点，并评估了其全局稳定性。此外，还得出了基本繁殖数（R0），以量化病毒的传播潜力。为确保模型的准确性，使用 MATLAB 并利用印度 COVID-19 的每日病例数据进行了数值模拟。参数值来源于现有文献，某些参数是通过将模型与观测数据进行拟合而估算出来的。最重要的是，该模型纳入了环境传播因素，如表面污染和空气传播。纳入这些因素后，人们对病毒传播有了更全面的了解，同时也证明了使用口罩、环境消毒、疫苗效力、治疗资源的可用性等干预措施的重要性，而这些因素在只关注人类直接接触的情况下被忽视了。研究还进行了敏感性分析，以评估不同参数对 R0 的影响，并通过热图直观显示结果，从而找出影响最大的因素。此外，还利用庞特里亚金的最大原则建立了一个最佳控制模型，从而制定出有效的干预策略。通过分析人际传播和环境传播机制，本研究为了解 SARS-CoV-2 传播提供了一个更全面的框架。所获得的洞察力对公共卫生战略的制定至关重要，强调了解决直接接触和环境传染源的必要性，从而更有效地控制当前和未来的疫情爆发。

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引用次数: 0

Association of selected gene variants with nonsyndromic orofacial clefts in Kuwait 科威特部分基因变异与非综合征口面裂的关系。

IF 2.6 3区生物学 Q2 GENETICS & HEREDITY

Gene

Pub Date : 2024-10-21 DOI: 10.1016/j.gene.2024.149028

Nada Abdelhafez , Amani Aladsani , Lateefa Alkharafi , Suzanne Al-Bustan

Introduction and objectives

Non-syndromic orofacial clefts (NSOFCs) are complex congenital abnormalities involving both environmental and genetic factors involved in orofacial development. This study aimed to investigate the genetic association of specific genetic variants at different CYRIA gene loci with the development of NSOFCs in Kuwait.

Methods

Four genetic variants (rs7552, rs3758249, rs3821949, and rs3917201) at four selected gene loci (CYRIA, FOXE1, MSX1, and TGFB3) were genotyped in a total of 240 DNA samples (patients (n = 114) and random controls (n = 126)) employing TaqMan® allele discrimination assay. For each variant and its genotype, the frequencies were determined and tested for Hardy-Weinberg Equilibrium. Genotype frequencies was compared between patients and controls using Pearson’s test. Logistic regression analyses were employed to test for the associations of the four selected variants with the occurrence of NSOFCSs.

Results

Significant differences in the distribution of genotypes between cases and controls, rs7552, rs3821949, and rs3917201 were found to have a positive association with NSOFCs. After adjusting for gender, the GG genotype of the rs7552 variant, the AG genotype of the rs3821949 variant, and the CC genotype of the rs3917201 variant showed nearly a two-fold increased risk of NSOFC (p < 0.05).

Conclusion

This study reports significant findings on the contribution and modest effect of CYRIA rs7552, MSX1 rs3821949, and TGFB3 rs3917201 in the development of NSOFCs. Our findings provide further evidence on the molecular mechanism and the role of the selected genes in NSOFCs.

导言和目的：非综合征性口面裂（NSOFCs）是一种复杂的先天性畸形，涉及口面部发育的环境和遗传因素。本研究旨在调查不同 CYRIA 基因位点的特定遗传变异与科威特 NSOFCs 发病的遗传关联：方法：采用 TaqMan® 等位基因鉴别检测法，对 240 份 DNA 样本（患者（n = 114）和随机对照（n = 126））中四个选定基因位点（CYRIA、FOXE1、MSX1 和 TGFB3）的四个基因变异（rs7552、rs3758249、rs3821949 和 rs3917201）进行基因分型。确定了每个变异及其基因型的频率，并进行了哈代-温伯格平衡测试。使用皮尔逊检验比较患者和对照组的基因型频率。采用逻辑回归分析来检验四个所选变异与 NSOFCS 发生的相关性：结果：病例与对照组之间的基因型分布存在显著差异，发现rs7552、rs3821949和rs3917201与NSOFCs呈正相关。在对性别进行调整后，rs7552 变体的 GG 基因型、rs3821949 变体的 AG 基因型和 rs3917201 变体的 CC 基因型的 NSOFC 风险增加了近 2 倍（p 结论：该研究报告了对 NSOFC 的贡献的重要发现：本研究报告了关于 CYRIA rs7552、MSX1 rs3821949 和 TGFB3 rs3917201 在 NSOFC 发病中的贡献和适度影响的重要发现。我们的研究结果为所选基因在 NSOFCs 中的分子机制和作用提供了进一步的证据。

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引用次数: 0

Ischemic stroke susceptibility associated with ALPK1 single nucleotide polymorphisms by inhibiting URAT1 in uric acid hemostasis 通过抑制尿酸止血过程中的 URAT1，发现缺血性中风易感性与 ALPK1 单核苷酸多态性有关。

IF 2.6 3区生物学 Q2 GENETICS & HEREDITY

Gene

Pub Date : 2024-10-20 DOI: 10.1016/j.gene.2024.149017

Luying Qiu , Xiaoqin Lu , Weishuang Xue , Hefei Fu , Shumin Deng , Long Li , Meilin Chen , Yanzhe Wang

Objectives

Ischemic stroke (IS) prevalence rising annually, the necessity of discovering non-interventional genetic influences is progressing. Single nucleotide polymorphism (SNP) plays a pivotal role in stable inheritance of disease susceptibility. Based on the relationship between Alpha- Kinase 1 (ALPK1) and traditional IS risk factors especially hyperuricemia, our study investigated the association and function of ALPK1 SNPs with IS susceptibility.

Methods

A case-control study of 1539 patients and 933 controls from northeast China was conducted. Genotyping information of ALPK1 rs2074379 and rs2074388 was collected. Four types of plasmids including rs2074379/rs2074388 G/G, A/G, G/A, and A/A were transfected into 293T cells to observe ALPK1 and SLC22A12 expression. Possible ALPK1 structures of different SNPs were predicted online.

Results

Genotype GG (OR = 1.371, CI = 1.029–1.828, P = 0.031) and GA (OR = 1.326, CI = 1.110–1.584, P = 0.002) of rs2074379 and GA of rs2074388 (OR = 1.359, CI = 1.137–1.624, P = 0.001) were found significantly susceptible to IS, with G allele on sites to be a risk allele. Rs2074379 had a multiplicative interaction with hyperuricemia (OR = 1.637, CI = 1.157–2.315, P = 0.005). Uric acid levels differed in genotypes (P < 0.001). The expression of ALPK1 (P < 0.01) and SLC22A12 in membrane urate transporter 1 (URAT1) protein (P < 0.05) functionally changed with G allele on either site. With glycine changing into aspartic acid at rs2074388, the protein secondary structure changed, but the ALPK1 protein subtype remained still.

Conclusions

ALPK1 rs2074379 and rs2074388 SNPs were functionally associated with IS susceptibility. The wild allele progressed IS risk probably by reducing ALPK1 expression and inhibiting URAT1 raising the uric acid level, contributing to further exploration of pathogenetic mechanisms of stroke.

Chinese Clinical Trial Registration number: ChiCTR-COC-17013559.

目的：缺血性脑卒中（IS）发病率逐年上升，发现非干预性遗传影响因素的必要性也在不断提高。单核苷酸多态性（SNP）在疾病易感性的稳定遗传中起着关键作用。基于α-激酶1（ALPK1）与传统的IS风险因素尤其是高尿酸血症之间的关系，我们的研究探讨了ALPK1 SNPs与IS易感性的关联和功能：方法：我们对中国东北地区的 1539 例患者和 933 例对照进行了病例对照研究。收集了 ALPK1 rs2074379 和 rs2074388 的基因分型信息。将 rs2074379/rs2074388 G/G、A/G、G/A 和 A/A 四种质粒转染至 293T 细胞，观察 ALPK1 和 SLC22A12 的表达。在线预测了不同SNP的ALPK1可能的结构：结果：发现rs2074379的基因型GG（OR = 1.371，CI = 1.029-1.828，P = 0.031）和GA（OR = 1.326，CI = 1.110-1.584，P = 0.002）以及rs2074388的基因型GA（OR = 1.359，CI = 1.137-1.624，P = 0.001）显著易感于IS，位点上的G等位基因是风险等位基因。Rs2074379 与高尿酸血症有乘法交互作用（OR = 1.637，CI = 1.157-2.315，P = 0.005）。尿酸水平在基因型中存在差异（P 结论：ALPK1 rs2074379 与高尿酸血症有多重交互作用：ALPK1 rs2074379和rs2074388 SNP与IS易感性有功能相关性。野生等位基因可能通过降低ALPK1表达和抑制URAT1提高尿酸水平来增加IS风险，有助于进一步探索脑卒中的发病机制。中国临床试验注册号：ChiCTR-COC-1701ChiCTR-COC-17013559。

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引用次数: 0

CircRNA expression profiling of the rat thalamus in temporomandibular joint chronic inflammatory pain 颞下颌关节慢性炎症性疼痛大鼠丘脑的 CircRNA 表达谱分析

IF 2.6 3区生物学 Q2 GENETICS & HEREDITY

Gene

Pub Date : 2024-10-20 DOI: 10.1016/j.gene.2024.149024

Haixia Deng , Pan Zhou , Jing Wang , Jie Zeng , Cong Yu

Orofacial pain (OFP) induced by temporomandibular disorders (TMDs) is prevalent, affecting approximately 4.6 % of the population. One specific type of TMD is temporomandibular osteoarthritis (TMJOA), a common degenerative disease that significantly impacts patients’ quality of life. Differentially expressed circular RNAs (DEcircRNAs) in the thalamus, which serves as a relay station in the orofacial pain transmission pathway, may play a crucial role and serve as potential target markers for inflammation and the progression of inflammatory pain in TMJOA. The aim of this study was to investigate the expression profile of circRNAs in the thalamus of TMJOA. We obtained the circRNA expression profile from the thalamus of a rat model of TMJOA through high-throughput sequencing (HT-seq) and further validated their expression using reverse transcription real-time polymerase chain reaction (RT-qPCR), followed by bioinformatics analysis of the expression data. A total of 425 circRNAs (DESeq2 p- value < 0.05, |log2FoldChange| > 0.0) were identified as significantly differentially expressed by RNA-Seq, comprising 188 up-regulated and 237 down-regulated circRNAs. After validation via RT-qPCR, we employed miRanda software to predict the binding sites of miRNAs for the identified circRNAs to further explore the functions of DEcircRNAs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed that DEcircRNAs were primarily enriched in pathways and functions related to synapse development, protein signaling and modification, ’Circadian entertainment’, the ’MAPK signaling pathway’, and ’Glutamatergic synapse’. These findings suggest that DEcircRNAs in the thalamus play a significant role in the progression of TMJOA and may serve as promising candidate molecular targets for gene therapy.

由颞下颌关节紊乱症（TMDs）引起的口面部疼痛（OFP）十分普遍，约占总人口的 4.6%。颞下颌关节骨关节炎（TMJOA）是TMD的一种特殊类型，是一种常见的退行性疾病，严重影响患者的生活质量。丘脑是口面部疼痛传导通路的中继站，丘脑中差异表达的环状 RNA（DEcircRNA）可能在 TMJOA 的炎症和炎症性疼痛进展中起着至关重要的作用，并可作为潜在的靶标。本研究旨在探讨 circRNA 在颞下颌关节疼痛丘脑中的表达谱。我们通过高通量测序（HT-seq）获得了颞下颌关节疼痛模型大鼠丘脑中的 circRNA 表达谱，并使用反转录实时聚合酶链反应（RT-qPCR）进一步验证了它们的表达，随后对表达数据进行了生物信息学分析。RNA-Seq共鉴定出425个circRNA（DESeq2 p值为0.0）具有显著差异表达，其中188个上调，237个下调。通过 RT-qPCR 验证后，我们利用 miRanda 软件预测了 miRNA 与所鉴定的 circRNAs 的结合位点，以进一步探索 DEcircRNAs 的功能。基因本体（GO）和京都基因组百科全书（KEGG）分析表明，DEcircRNAs主要富集在与突触发育、蛋白质信号转导和修饰、"昼夜节律娱乐"、"MAPK信号通路 "和 "谷氨酸能突触 "相关的通路和功能中。这些研究结果表明，丘脑中的 DEcircRNAs 在颞下颌关节缺失症的进展过程中起着重要作用，可作为基因治疗的候选分子靶点。

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引用次数: 0

Insights into disease resilience and longevity: Hints from COVID-19 recovered nonagenarians and centenarians 疾病复原力和长寿的启示：COVID-19 复原的非长寿者和百岁老人的提示。

IF 2.6 3区生物学 Q2 GENETICS & HEREDITY

Gene

Pub Date : 2024-10-20 DOI: 10.1016/j.gene.2024.149025

Mateus V. de Castro , Cristina Sábato , Raíssa M. Dandalo-Girardi , Monize V.R. Silva , Luiz P. Dell’Aquila , Álvaro Razuk-Filho , Pedro B. Batista-Júnior , Michel S. Naslavsky , Mayana Zatz

The effects of aging on the organism manifest in various ways, including profound and complex changes in functioning patterns, responses to stimuli, and regenerative capacity. Nevertheless, it is remarkable that some elderly individuals maintain their health and functionality despite advanced age, showing resilience to environmental adversities, such as SARS-CoV-2 infection. In this study, we examined a unique cohort of 100 individuals older than 90 years, including centenarians, who recovered from COVID-19 before the availability of vaccines in Brazil. We performed whole-exome analyses and identified incidental findings in four participants. These findings included pathogenic variants associated with serious conditions, such as cancer predisposition and cardiovascular diseases. Specifically, variants were found in the RYR1, DSP, BRCA2, BRCA1, and TTN genes. Also, other two individuals were homozygous for rare variants in the TYK2 gene, related to primary immunodeficiencies. The significance of these findings is underscored by the fact that, despite carrying these rare variants, these individuals surpassed 90 years of age and survived the COVID-19 pandemic. This suggests the presence of genetic protective factors that contribute to longevity and resilience. Therefore, this study provides new insights into interpreting incidental findings in long-lived populations and raises important questions for clinical practice and the genetics of longevity.

衰老对机体的影响是多方面的，包括机能模式、对刺激的反应和再生能力等方面深刻而复杂的变化。然而，令人瞩目的是，一些老年人尽管年事已高，但仍能保持健康和机能，对环境逆境（如 SARS-CoV-2 感染）表现出顽强的抵抗力。在这项研究中，我们研究了一个独特的队列，该队列由 100 名 90 岁以上的老年人组成，其中包括百岁老人。我们进行了全外显子组分析，发现了四名参与者的偶然发现。这些发现包括与癌症易感性和心血管疾病等严重疾病相关的致病变异。具体来说，在 RYR1、DSP、BRCA2、BRCA1 和 TTN 基因中发现了变异。另外，还有两个人是 TYK2 基因罕见变异的同卵双生者，这与原发性免疫缺陷有关。尽管携带这些罕见变异基因，但这些人的年龄都超过了 90 岁，并在 COVID-19 大流行中存活下来，这一事实凸显了这些发现的重要性。这表明存在有助于长寿和恢复能力的遗传保护因素。因此，这项研究为解释长寿人群的偶然发现提供了新的见解，并为临床实践和长寿遗传学提出了重要问题。

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引用次数: 0

Investigating SNHG3 as a potential therapeutic approach for HCC stem cells. 研究 SNHG3 作为治疗 HCC 干细胞的潜在方法。

IF 2.6 3区生物学 Q2 GENETICS & HEREDITY

Gene

Pub Date : 2024-10-19 DOI: 10.1016/j.gene.2024.149022

Dingmao Wang, Xiao Yu, Yijun Yang

Introduction: Hepatocellular Carcinoma (HCC) is a common malignant tumor worldwide. Long Non-Coding RNA (lncRNA) has gained attention in tumor biology, and this study aims to investigate the role of lncRNA SNHG3 in HCC, specifically in the self-renewal and maintenance of liver cancer stem cells.

Methods: The expression of lncRNA SNHG3 was analyzed in HCC and adjacent normal tissue using the TCGA database. The expression levels of SNHG3 in HCC cell lines (Hep3B, HepG2, Huh7) were detected using qRT-PCR and Western blot techniques. Functional assays, including CCK-8, soft agar colony formation, and tumor sphere formation, were performed to evaluate the impact of SNHG3 on HCC stem cell functionality. MeRIP-qPCR was also used to investigate the regulatory role of SNHG3 in m6A modification of ITGA6 mRNA mediated by METTL3.

Results: The study found that SNHG3 was significantly upregulated in HCC tissue and cell lines compared to normal liver tissue. SNHG3 expression correlated with the pathological stage, metastasis status, and tumor size of liver cancer. Inhibiting SNHG3 reduced proliferation, colony formation, and tumor sphere formation ability in HCC stem cells. SNHG3 also played a role in regulating the m6A modification and expression of ITGA6 through METTL3.

Conclusion: This study emphasizes the upregulation of lncRNA SNHG3 and its role in HCC stem cell self-renewal. SNHG3 may regulate the m6A modification of ITGA6 mRNA through its interaction with METTL3, impacting the function of liver cancer stem cells. These findings support the potential of targeting SNHG3 as a therapeutic approach for HCC.

简介肝细胞癌（HCC）是全球常见的恶性肿瘤。本研究旨在探讨lncRNA SNHG3在HCC中的作用，特别是在肝癌干细胞自我更新和维持中的作用：方法：利用TCGA数据库分析lncRNA SNHG3在HCC和邻近正常组织中的表达。采用 qRT-PCR 和 Western 印迹技术检测 SNHG3 在 HCC 细胞系（Hep3B、HepG2、Huh7）中的表达水平。为评估SNHG3对HCC干细胞功能的影响，进行了包括CCK-8、软琼脂集落形成和肿瘤球形成在内的功能测试。研究还利用MeRIP-qPCR技术研究了SNHG3在METTL3介导的ITGA6 mRNA m6A修饰中的调控作用：研究发现，与正常肝组织相比，SNHG3在HCC组织和细胞系中明显上调。SNHG3的表达与肝癌的病理分期、转移状态和肿瘤大小相关。抑制 SNHG3 可降低 HCC 干细胞的增殖、集落形成和肿瘤球形成能力。SNHG3还通过METTL3在调控ITGA6的m6A修饰和表达方面发挥作用：本研究强调了lncRNA SNHG3的上调及其在HCC干细胞自我更新中的作用。SNHG3可能通过与METTL3的相互作用调控ITGA6 mRNA的m6A修饰，从而影响肝癌干细胞的功能。这些发现支持了靶向SNHG3作为HCC治疗方法的潜力。

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引用次数: 0

Strong associations between the FGF-2 gene and productivity traits of Holstein-Friesian dairy cattle. FGF-2 基因与荷斯坦-弗里斯兰奶牛的生产性能之间存在密切联系。

IF 2.6 3区生物学 Q2 GENETICS & HEREDITY

Gene

Pub Date : 2024-10-19 DOI: 10.1016/j.gene.2024.149027

Mustafa Kibar, İbrahim Aytekin

Sustainability in dairy cattle farms depends on the efficiency of milk yield and reproductive traits. Thus, this study aimed to investigate the effect of the FGF-2/Csp6I gene and major environmental factors on these traits in Holstein-Friesian cattle. A total of 212 whole blood samples were collected from the Vena coccygea of cattle and the data obtained from these samples were used in all statistical analyses. Then, the restriction fragment length polymorphism (RFLP) method (determination of genotypes) was conducted and programs including PopGene (allele and genotype frequencies), Minitab (association analyses) and MTDFREML (variance components and genetic parameters) were used. Alleles A (0.4269) and G (0.5731) as well as genotypes AA (0.174), AG (0.505) and GG (0.321) were found, indicating that the population is polymorphic and in Hardy-Weinberg equilibrium (P > 0.05). The effect of the Csp6I polymorphism of FGF-2 gene on peak milk yield (PMY) (P < 0.01); lactation milk yield (LMY), milking time (MT), 305-day and 200-day lactation milk yield (LMY₃₀₅ and LMY₂₀₀), average daily milk yield (ADMY) (P < 0.05); 100-day lactation milk yield (LMY₁₀₀), age of using in first breeding (AUFB) and number of inseminations per conception (NIPC) (P < 0.10) were significant. The heritability of milk yield traits and the correlation between direct and maternal heritability for reproductive traits were high. Furthermore, the breeding value of PMY was higher for the AA genotype (0.745 ± 0.292) than for the AG genotype (-0.268 ± 0.171) (P < 0.05). As a result, the A allele and AA genotype for the FGF-2/Csp6I gene had an increasing effect on milk yield without compromising reproductive performance in Holstein-Friesian dairy cattle.

奶牛场的可持续性取决于产奶量和繁殖性状的效率。因此，本研究旨在调查 FGF-2/Csp6I 基因和主要环境因素对荷斯坦-弗里斯兰牛这些性状的影响。研究人员从牛的尾静脉采集了 212 份全血样本，并将从这些样本中获得的数据用于所有统计分析。然后，采用限制性片段长度多态性（RFLP）方法（确定基因型），并使用 PopGene（等位基因和基因型频率）、Minitab（关联分析）和 MTDFREML（方差成分和遗传参数）等程序。结果发现，等位基因 A (0.4269) 和 G (0.5731) 以及基因型 AA (0.174)、AG (0.505) 和 GG (0.321)，表明该群体具有多态性，且处于哈代-温伯格平衡状态（P > 0.05）。FGF-2 基因 Csp6I 多态性对高峰产奶量（PMY）（P 305 和 LMY200）、平均日产奶量（ADMY）（P 100）、首次配种使用年龄（AUFB）和每次受精次数（NIPC）的影响（P

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引用次数: 0

Berberine: A multifaceted agent for lung cancer treatment-from molecular insight to clinical applications 小檗碱：肺癌治疗的多面手--从分子洞察到临床应用。

IF 2.6 3区生物学 Q2 GENETICS & HEREDITY

Gene

Pub Date : 2024-10-19 DOI: 10.1016/j.gene.2024.149021

Xiaodan Xu , Yuanyuan He , Jungang Liu

Lung cancer is a major cause of cancer-related deaths worldwide, and it poses a significant threat to global health due to its high incidence and mortality rates. There is an urgent need for better prevention, early detection, and effective treatments for this disease. The treatment options for lung cancer depend on various factors such as the stage of the disease, the type of cancer, and the patient’s overall health. Currently, the primary treatment strategies include surgery, chemotherapy, radiation therapy, targeted therapy, immunotherapy, and combination therapies. Berberine, a natural alkaloid found in medicinal plants, has demonstrated potential as an effective anti-cancer agent against lung cancer. The present study aims to summarize the evidence supporting Berberine’s ability to inhibit the growth of lung cancer cells, induce apoptosis, and slow down tumor growth in both laboratory and animal studies. The study also shed light on the complex molecular mechanisms involved in its anti-tumor effects, including its impact on signaling pathways, DNA repair systems, and interaction with non-coding RNAs, all of which contribute to tumor suppression. Additionally, the synergistic effects of Berberine with other natural compounds and chemotherapy drugs are discussed. Overall, its multifaceted approach and proven effectiveness justify further research to develop Berberine into a viable treatment option for lung cancer patients.

Abbreviations: BBR, Berberine; EMT, epithelial-mesenchymal transition; NSCLC, non-small cell lung cancer; ROS, reactive oxygen species; ASK1, Apoptosis Signal-regulating Kinase 1; JNK, c-Jun N-terminal kinase; BHC, Berberine Hydrochloride; DSB, double-strand breaks; CSN, COP9 signalosome; NIR, near-infrared; LLC, Lewis lung carcinoma; RTK, receptor tyrosine kinase; B-Phyt-LCNs, Berberine-Phytantriol liquid crystalline nanoparticles; ER, endoplasmic reticulum; Ber-LCNs, Berberine-loaded liquid crystalline nanoparticles; BNS, Berberine nanostructure; BER-CS-NPs, Berberine-loaded chitosan nanoparticles; B-Phyt-LCNs, Berberine-Phytantriol liquid crystalline nanoparticles; B-Phyt-LCNs, Berberine-loaded liquid crystalline nanoparticles; Ber-LCNs, Berberine-loaded liquid crystalline nanoparticles; B-ZnO NPs, Berberine-loaded zinc oxide nanoparticles; B-C60, Berberine-C60 complex; LTP, Low-Temperature Plasma.

肺癌是全球癌症相关死亡的主要原因，由于其发病率和死亡率都很高，它对全球健康构成了重大威胁。人们迫切需要更好地预防、早期发现和有效治疗这种疾病。肺癌的治疗方案取决于各种因素，如疾病的阶段、癌症的类型以及患者的整体健康状况。目前，主要的治疗策略包括手术、化疗、放疗、靶向治疗、免疫治疗和综合疗法。小檗碱是一种存在于药用植物中的天然生物碱，已被证明是一种有效的肺癌抗癌剂。本研究旨在总结小檗碱在实验室和动物实验中抑制肺癌细胞生长、诱导细胞凋亡和减缓肿瘤生长的证据。研究还揭示了小檗碱抗肿瘤作用所涉及的复杂分子机制，包括对信号通路、DNA 修复系统的影响，以及与非编码 RNA 的相互作用，所有这些都有助于抑制肿瘤。此外，还讨论了小檗碱与其他天然化合物和化疗药物的协同作用。总之，小檗碱的多面性和经证实的有效性证明了进一步研究小檗碱成为肺癌患者可行治疗方案的合理性。缩写：缩写：BBR，小檗碱；EMT，上皮-间质转化；NSCLC，非小细胞肺癌；ROS，活性氧；ASK1，凋亡信号调节激酶 1；JNK，c-Jun N-末端激酶；BHC，盐酸小檗碱；DSB，双链断裂；CSN，COP9 信号体；NIR，近红外；LLC，路易斯肺癌；RTK，受体酪氨酸激酶；B-Phyt-LCNs，小檗碱-泛醇液晶纳米颗粒；ER，内质网；BER-CS-NPs，小檗碱负载壳聚糖纳米颗粒；B-Phyt-LCNs，小檗碱-植物三醇液晶纳米颗粒；B-Phyt-LCNs，小檗碱负载液晶纳米颗粒；Ber-LCNs，小檗碱负载液晶纳米颗粒；B-ZnO NPs，小檗碱负载氧化锌纳米颗粒；B-C60，小檗碱-C60 复合物；LTP，低温等离子体。

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Investigation of chromatin remodeling-related biomarkers and associated molecular mechanism in pulpitis 研究牙髓炎中染色质重塑相关生物标志物及相关分子机制。

IF 2.6 3区生物学 Q2 GENETICS & HEREDITY

Gene

Pub Date : 2024-10-19 DOI: 10.1016/j.gene.2024.149016

Chenglin Li, Yujiao Sun

The current study aimed to identify potential chromatin remodeling-related biomarkers and the associated molecular mechanisms in pulpitis. Differentially expressed genes associated with chromatin remodeling (DECRGs) were identified using datasets from an online database. Enrichment and protein–protein interaction (PPI) network analyses were performed based on the DECRGs to identify biomarkers for pulpitis, followed by GSEA (gene set enrichment analysis). The diagnostic value of these biomarkers were evaluated by ROC (Receiver operating characteristic) and nomogram investigation. Next, microRNA(miRNA)-mRNA-TF (transcription factor), ceRNA (competing endogenous RNA), and drug prediction networks were constructed based on the biomarkers. Finally, reverse transcription-real-time quantitative PCR analysis and western blot were performed to validate the results of the bioinformatic analysis. This study identified 87 DECRGs between pulpitis and normal dental pulp samples that were mainly enriched in chromatin remodeling functions and pathways in cancer. A PPI network identified five biomarkers: TNF, STAT3, MYC, ACTB, and MAPK8. ROC and nomogram analyses demonstrated the diagnostic value of these biomarkers. GSEA of biomarkers such as STAT3 was mainly enriched in functions such as the B cell receptor signaling pathway. A biomarker-disease network and miRNA-mRNA-TF interactions were constructed using these biomarkers. A ceRNA network was constructed with interactions including chr22-38_28785274-29006793.1-miR-125b-5p-STAT3. A drug-gene network was established using 170 drugs and five biomarkers. Finally, qRT-PCR was used to validate the expression of all five biomarkers identified by the bioinformatics analysis. TNF, STAT3, MYC, ACTB, and MAPK8 are potential chromatin remodeling-related diagnostic markers for pulpitis. Moreover, long non-coding RNA (lncRNA) chr22-38_28785274-29006793.1 might function as a ceRNA to regulate the expression of the chromatin remodeling gene STAT3 by sponging miR-125b-5p in pulpitis.

本研究旨在确定潜在的染色质重塑相关生物标志物以及牙髓炎的相关分子机制。研究人员利用在线数据库中的数据集确定了与染色质重塑相关的差异表达基因（DECRGs）。根据DECRGs进行了富集和蛋白-蛋白相互作用（PPI）网络分析，以确定牙髓炎的生物标志物，然后进行了GSEA（基因组富集分析）。通过ROC（Receiver operating characteristic，接收者操作特征）和提名图调查评估了这些生物标志物的诊断价值。然后，根据这些生物标志物构建了微RNA（miRNA）-mRNA-TF（转录因子）、ceRNA（竞争性内源性RNA）和药物预测网络。最后，进行了反转录实时定量 PCR 分析和 Western 印迹，以验证生物信息分析的结果。这项研究在牙髓炎样本和正常牙髓样本之间发现了87个DECRGs，它们主要富集于染色质重塑功能和癌症通路。PPI网络确定了五个生物标志物：TNF、STAT3、MYC、ACTB 和 MAPK8。ROC和提名图分析表明了这些生物标志物的诊断价值。STAT3等生物标志物的GSEA主要富集在B细胞受体信号通路等功能中。利用这些生物标记物构建了生物标记物-疾病网络和 miRNA-mRNA-TF 相互作用。利用包括 chr22-38_28785274-29006793.1-miR-125b-5p-STAT3 在内的相互作用构建了一个 ceRNA 网络。利用 170 种药物和 5 个生物标记物建立了药物基因网络。最后，利用 qRT-PCR 验证了生物信息学分析确定的所有五个生物标志物的表达。TNF、STAT3、MYC、ACTB和MAPK8是潜在的染色质重塑相关的牙髓炎诊断标志物。此外，长非编码RNA（lncRNA）chr22-38_28785274-29006793.1可能作为一种ceRNA，在牙髓炎中通过疏导miR-125b-5p来调节染色质重塑基因STAT3的表达。

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